Long-Term Ovarian Cancer Survival Associated With Mutation in BRCA1 or BRCA2

John R. McLaughlin; Barry Rosen; Joel Moody; Tuya Pal; Isabel Fan; Patricia A. Shaw; Harvey A. Risch; Thomas A. Sellers; Ping Sun; Steven A. Narod

Disclosures

J Natl Cancer Inst. 2013;105(2):141-148. 

In This Article

Abstract and Introduction

Abstract

Background Studies have suggested that the 5-year survival of women with ovarian cancer and a BRCA1 or BRCA2 mutation is better than expected. We sought to evaluate the impact of carrying a BRCA1 or BRCA2 mutation on long-term survival of women after a diagnosis of invasive ovarian cancer.
Methods One thousand six hundred twenty-six unselected women diagnosed with invasive ovarian cancer in Ontario, Canada, or in Tampa, Florida, between 1995 and 2004 were followed for a mean of 6.9 years (range = 0.3 to 15.7 years). Mutation screening for BRCA1 and BRCA2 revealed mutations in 218 women (13.4%). Left-truncated survival analysis was conducted to estimate ovarian cancer–specific survival at various time points after diagnosis for women with and without mutations.
Results In the 3-year period after diagnosis, the presence of a BRCA1 or BRCA2 mutation was associated with a better prognosis (adjusted hazard ratio = 0.68, 95% confidence interval [CI] = 0.48 to 0.98; P = .03), but at 10 years after diagnosis, the hazard ratio was 1.00 (95% CI = 0.83 to 1.22; P = .90). Among women with serous ovarian cancers, 27.4% of women who were BRCA1 mutation carriers, 27.7% of women who were BRCA2 carriers, and 27.1% of women who were noncarriers were alive at 12 years past diagnosis.
Conclusion For women with invasive ovarian cancer, the short-term survival advantage of carrying a BRCA1 or BRCA2 mutation does not lead to a long-term survival benefit.

Introduction

The majority of women diagnosed with invasive ovarian cancer in Canada or the United States will succumb to their disease, but approximately 35% of women with ovarian cancer (including 20% of patients with serous cancers) are expected to be long-term survivors and ultimately cured.[1] Overall, 13% of unselected case patients of ovarian cancer are attributable to mutations in BRCA1 or BRCA2.[2,3] Several studies have examined survival after ovarian cancer for women with BRCA1 or BRCA2 mutations,[4–14] and most report better survival for women with mutations.[4,6–14] Observed differences in survival may be the result of differences in the intrinsic aggressiveness of hereditary vs nonhereditary cancers, differences in the ages of diagnosis and/or histologic subtypes, or differences in the response to chemotherapy. Many studies published to date have followed case patients for relatively short periods of time. This approach is valid if the relative hazard associated with a gene mutation is constant over time, but if the assumption of hazards proportionality is violated, then a long period of follow-up is necessary to permit proper comparison of survivorship. In many studies, the hereditary case patients and the group of comparison patients were derived from different populations.[5,6,9,11,13,14] Additionally, many studies involved less than 50 hereditary case patients,[4,7–9,12] and some studies did not properly adjust for survivorship bias.[5,11–13] We sought to estimate 10-year survival for women with ovarian cancer, with and without mutations in BRCA1 or BRCA2, to determine whether or not the observed short-term survival benefit for mutation carriers is associated with a better prospect for cure.

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